Chromosome Deletion Predicts Aggressive Neuroblastoma

Edward F. Attiyeh, M.D., a pediatric oncology fellow at The Children's Hospital of Philadelphia, reported on a study of 915 patients in a presentation today at the American Society of Clinical Oncology annual meeting in Orlando, Fla. The patients were children with primary neuroblastoma treated at Children's Oncology Group (COG) centers. The COG is a National Institutes of Health-funded multicenter clinical research organization that supports clinical trials for pediatric cancer patients.

Neuroblastoma, which accounts for 10 percent of all pediatric cancers, often occurs as a solid tumor in a child's abdomen or chest. Some cases of neuroblastoma are low risk, and resolve after surgeons remove the tumor. Other cases are more aggressive, and are more likely to resist initial treatment, or to cause a relapse. Identifying the correct risk level allows doctors to treat aggressive cancers appropriately, while not subjecting children with low-risk cancer to overtreatment.

Oncologists know that amplification, an abnormal increase in the number of copies, of a cancer-causing gene called MYCN heralds a high-risk, aggressive cancer. However, a significant number of neuroblastomas are aggressive without having amplified MYCN. "The deletion of genetic material on chromosome 11 may account for a significant percentage of these high-risk neuroblastomas," said Dr. Attiyeh.

It is unknown what causes the deletion of genes on chromosome 11, at a location designated chromosome 11q23. However, the loss of material at that site apparently removes the protective effect of a tumor suppressor gene, and thereby allows the tumor to grow. Patients in the study with the chromosome deletion had a three-year overall survival rate of 66 percent, compared to 83 percent for patients without the deletion.

Dr. Attiyeh's research abstract received top honors at the ASCO meeting, by being named the top abstract among more than 100 submitted by oncology fellows. It also received a second award, as the highest-ranking abstract in pediatric cancer research. Dr. Attiyeh works in a comprehensive neuroblastoma research program at Children's Hospital, directed by John M. Maris, M.D., the senior author of the abstract.

Co-authors of the study, in addition to Drs. Attiyeh and Maris, included Katherine K. Matthay, M.D., of the University of California, San Francisco; and Yael P. Mosse, M.D., of The Children's Hospital of Philadelphia.

About the Oncology Program at The Children's Hospital of Philadelphia: The Children's Hospital of Philadelphia cares for more children with cancer than any other general pediatric hospital in the United States. Its extensive basic and clinical research programs have been recognized recently by Child Magazine, which ranked Children's Hospital first in the nation in pediatric oncology. In the field of neuroblastoma, Garrett Brodeur, M.D., chief of Oncology, has been a pioneer in developing international standards for risk stratification as a guide to neuroblastoma treatment. John M. Maris, M.D., directs a neuroblastoma research laboratory with seven projects focusing on comprehensive translational research. Stephan Grupp, M.D., Ph.D., has pioneered the use of tandem stem cell transplants for children with high-risk neuroblastoma, and has achieved some of the best results ever published in treating these patients.

The Children's Hospital of Philadelphia was founded in 1855 as the nation's first pediatric hospital. Through its long-standing commitment to providing exceptional patient care, training new generations of pediatric healthcare professionals and pioneering major research initiatives, Children's Hospital has fostered many discoveries that have benefited children worldwide. Its pediatric research program is among the largest in the country, ranking second in National Institutes of Health funding. In addition, its unique family-centered care and public service programs have brought the 430-bed hospital recognition as a leading advocate for children and adolescents. For more information, visit www.chop.edu.